Characterization of the inhibitor-resistant SHV β-lactamase SHV-107 in a clinic...

• Autor(es): Manageiro, Vera ; Ferreira, Eugénia ; Cougnoux, Antony ; Albuquerque, Luís ; Caniça, Manuela ; Bonnet, Richard
• Data: 2012
• Identificador Persistente: http://hdl.handle.net/10400.18/1381
• Origem: Repositório Científico do Instituto Nacional de Saúde
• Assunto(s): Antibiotic Resistance; β-lactam Inhibitor; β-lactamase; ESBL; Inhibitor-resistant SHV; Resistência aos Antimicrobianos
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

The clinical Klebsiella pneumoniae INSRA6884 strain exhibited nonsusceptibility to all penicillins tested (MICs of 64 to>2,048 g/ml). The MICs of penicillins were weakly reduced by clavulanate (from 2,048 to 512 g/ml), and tazobactam restored piperacillin susceptibility. Molecular characterization identified the genes blaGES-7 and a new -lactamase gene, blaSHV-107, which encoded an enzyme that differed from SHV-1 by the amino acid substitutions Leu35Gln and Thr235Ala. The SHV-107-producing Escherichia coli strain exhibited only a -lactam resistance phenotype with respect to amoxicillin, ticarcillin, and amoxicillinclavulanate combination. The kinetic parameters of the purified SHV-107 enzyme revealed a high affinity for penicillins. However, catalytic efficiency for these antibiotics was lower for SHV-107 than for SHV-1. No hydrolysis was detected against oxyimino- -lactams. The 50% inhibitory concentration (IC50) for clavulanic acid was 9-fold higher for SHV-107 than for SHV-1, but the inhibitory effects of tazobactam were unchanged. Molecular dynamics simulation suggested that the Thr235Ala substitution affects the accommodation of clavulanate in the binding site and therefore its inhibitory activity.